Download 2016 Update to Heart Failure Clinical Practice Guidelines

2016 Update to Heart Failure
Clinical Practice Guidelines
Tuesday August 2, 2016
1:00pm – 2:00pm CST (60 minute webinar)
Presenters:
Dr. Gregg Fonarow, MD, FACC, FAHA, FHFSA
Dr. Clyde Yancy, MD, MSc, MACC, FAHA, MACP
Dr. Paul Heidenreich, MD, MS, FACC
Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP
Vice Dean, Diversity & Inclusion
Magerstadt Professor of Medicine
Professor of Medical Social Sciences
Chief, Division of Cardiology
Northwestern University, Feinberg School of Medicine
Associate Director, Bluhm Cardiovascular Institute
8/2/2016
Gregg C. Fonarow, MD, FACC, FAHA
Paul A Heidenreich, MD, MS,
The Eliot Corday Professor of Cardiovascular Medicine and
Science
Co-Chief of Clinical Cardiology UCLA Division of
Cardiology
Director, Ahmanson-UCLA Cardiomyopathy Center
Co-Director, UCLA Preventative Cardiology Program
Associate Professor of Medicine
Vice-Chair for Clinical, Quality and Analytics,
Department of Medicine
Stanford University
FACC
©2013, American Heart Association
2
2016 Update to Heart Failure Clinical Practice Guidelines
• New Epidemiology
• New Therapies
• New Guidelines
• New Phenotype
From: A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010
JAMA Intern Med. 2015;175(6):996-1004. doi:10.1001/jamainternmed.2015.0924
Figure Legend:
Temporal Trends in Heart Failure Incidence Rates Overall and by Reduced or Preserved Ejection Fraction Among Women and Men
in Olmsted County, Minnesota, 2000 to 2010Yearly rates (smoothed using 3-year moving average) per 100 000 persons have been
standardized by the direct method to the age distribution of the US population in 2010. HFpEF indicates heart failure with preserved
ejection fraction; HFrEF, heart failure with reduced ejection fraction.
Date of download: 6/10/2016
Copyright © 2016 American Medical
Association. All rights reserved.
A Contemporary Appraisal of the HF Epidemic
•
Age and sex-specific incidence of heart failure has declined
– 315/100,000 to 219/100,000
•
Rate reduction of 37.5%
•
Incidence decline was greater for HFrEF – 45.1% vs. HFpEF -27.9%
•
Risk for CV death was lower for HFpEF but the same for non-CV death
•
Hospitalizations have increased 34%
•
Most hospitalizations, 63%, were due to non-cardiovascular causes
•
Thus today’s epidemic of heart failure is defined by a marked increase in
hospitalizations, predominance of non-CV death rate, and persistence and
predominance of HFpEF
Roger VL et al. JAMA Intern Med. 2015; April 20. Epub ahead of print.
Stages, Phenotypes and Treatment of HF
At Risk for Heart Failure
STAGE B
STAGE A
At high risk for HF but
without structural heart
disease or symptoms of HF
e.g., Patients with:
• HTN
• Atherosclerotic disease
• DM
• Obesity
• Metabolic syndrome
or
Patients
• Using cardiotoxins
• With family history of
cardiomyopathy
THERAPY
Heart Failure
STAGE C
Structural heart disease
but without signs or
symptoms of HF
Structural heart
disease
e.g., Patients with:
• Previous MI
• LV remodeling including
LVH and low EF
• Asymptomatic valvular
disease
THERAPY
Goals
• Heart healthy lifestyle
• Prevent vascular,
coronary disease
• Prevent LV structural
abnormalities
Goals
• Prevent HF symptoms
• Prevent further cardiac
Drugs
• ACEI or ARB in
appropriate patients for
vascular disease or DM
• Statins as appropriate
appropriate
• Beta blockers as
appropriate
remodeling
Drugs
• ACEI or ARB as
In selected patients
• ICD
• Revascularization or
valvular surgery as
appropriate
STAGE D
Structural heart disease
with prior or current
symptoms of HF
Development of
symptoms of HF
Refractory HF
Refractory
symptoms of HF
at rest, despite
GDMT
e.g., Patients with:
• Known structural heart disease and
• HF signs and symptoms
HFpEF
HFrEF
THERAPY
THERAPY
Goals
• Control symptoms
• Improve HRQOL
• Prevent hospitalization
• Prevent mortality
Strategies
• Identification of comorbidities
Treatment
• Diuresis to relieve symptoms
of congestion
• Follow guideline driven
indications for comorbidities,
e.g., HTN, AF, CAD, DM
• Revascularization or valvular
surgery as appropriate
Goals
• Control symptoms
• Patient education
• Prevent hospitalization
• Prevent mortality
Drugs for routine use
• Diuretics for fluid retention
• ACEI or ARB
• Beta blockers
• Aldosterone antagonists
Drugs for use in selected patients
• Hydralazine/isosorbide dinitrate
• ACEI and ARB
• Digoxin
In selected patients
• CRT
• ICD
• Revascularization or valvular
surgery as appropriate
e.g., Patients with:
• Marked HF symptoms at
rest
• Recurrent hospitalizations
despite GDMT
THERAPY
Goals
• Control symptoms
• Improve HRQOL
• Reduce hospital
readmissions
• Establish patient’s endof-life goals
Options
• Advanced care
measures
• Heart transplant
• Chronic inotropes
• Temporary or permanent
MCS
• Experimental surgery or
drugs
• Palliative care and
hospice
• ICD deactivation
Yancy, C. Jessup M, Bozkurt B. et al. JACC 2013
Pharmacologic Treatment for Stage C HFrEF
HFrEF Stage C
NYHA Class I – IV
Treatment:
Class I, LOE A
ACEI or ARB AND
Beta Blocker
For all volume overload,
NYHA class II-IV patients
For persistently symptomatic
African Americans,
NYHA class III-IV
For NYHA class II-IV patients.
Provided estimated creatinine
>30 mL/min and K+ <5.0 mEq/dL
Add
Add
Add
Class I, LOE C
Loop Diuretics
Class I, LOE A
Hydral-Nitrates
Class I, LOE A
Aldosterone
Antagonist
Yancy, C et al. JACC 2013
Residual Risk for HFrEF Despite
Conventional GDMT
Of all patients randomized to enalapril, the
absolute risk of CV death as a first event
was 10.9% (n=459/4212)1
In PARADIGM-HF, study patients were followed over a median of 27 months.2,*
*Adult patients with NYHA class II–IV symptoms and an ejection fraction of 40% or
less were required to take a stable dose of a beta blocker and an ACE inhibitor (or
ARB) equivalent to at least 10 mg of enalapril daily, with most also receiving MRA.
McMurray J et al. N Engl J Med. 2014;371:993-1004.
Effects of Neprilysin Inhibition in Heart Failure
Neurohormonal
activation
Endogenous
vasoactive peptides
Vascular tone
(natriuretic peptides, adrenomedullin,
bradykinin, substance P,
calcitonin gene-related peptide)
Cardiac fibrosis,
hypertrophy
Sodium retention
Neprilysin
Neprilysin
inhibition
Inactive metabolites
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
PARADIGM-HF: Primary Endpoint of CV Death or Heart
Failure Hospitalization
Number needed to treat = 21
Cumulative Probability
1.0
HR 0.80 (95% CI,
0.73–0.87), p<0.001
0.6
0.5
0.4
0.3
0.2
0.1
0
Enalapril
1117 events (26.5%)
Sac/Val
914 events (21.8%)
0
180 360 540 720 900 1080 1260
Days since Randomization
Number at
4187 3922 3663
Risk
4212 3883 3579
Sac/Val
Enalapril
3018 2257 1544
2922 2123 1488
896
853
249
236
Sac/Val = Sacubitril/Valsartan.
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
PARADIGM-HF: Effect of Sac/Val vs. Enalapril on the
Primary Endpoint and Its Components
Sac/Val
(n=4187)
Enalapril
(n=4212)
Hazard Ratio
(95% CI)
pValue
Primary
endpoint
914
(21.8%)
1117
(26.5%)
0.80
(0.73–0.87)
<0.001
Cardiovascular
death
558
(13.3%)
693
(16.5%)
0.80
(0.71–0.89)
<0.001
Hospitalization
for heart failure
537
(12.8%)
658
(15.6%)
0.79
(0.71–0.89)
<0.001
Sac/Val = Sacubitril/Valsartan.
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
Sac/Val vs. Enalapril on Primary Endpoint and on CV Death by
Subgroups
Subgroup
Sac/Val Enalapril
No.
All Patients
Age
<65 years
≥65 years
Sex
Male
Female
NYHA Class
I or II
III or IV
Estimated GFR
<60 mL/min/1.73 m2
≥60 mL/min/1.73 m2
Ejection fraction
≤35%
>35%
NT-proBNP
≤Median
>Median
Hypertension
No
Yes
Prior use of ACE inhibitor
No
Yes
Prior use of aldosterone antagonist
No
Yes
Prior hospitalization for heart failure
No
Yes
Primary Endpoint
Hazard Ratio
(95% CI)
Death from Cardiovascular Causes
p-Value for
Interaction
Hazard Ratio
(95% CI)
p-Value for
Interaction
4187
4212
2111
2076
2168
2044
0.47
0.70
3308
879
3259
953
0.63
0.92
3187
1002
3130
1076
0.03
0.76
1541
2646
1520
2692
0.91
0.73
3715
472
3722
489
0.36
0.36
2079
2103
2116
2087
0.16
0.33
1218
2969
1241
2971
0.87
0.14
921
3266
946
3266
0.09
0.06
1916
2271
1812
2400
0.10
0.32
1580
2607
1545
2667
0.10
0.19
0.3 0.5 0.7 0.9 1.1 1.3 1.5 1.7
0.3 0.5 0.7 0.9 1.1 1.3 1.5 1.7
Sac/Val Better
Sac/Val Better
Enalapril Better
Enalapril Better
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
PARADIGM-HF: Adverse Events
Sac/Val
(n=4187)
Enalapril
(n=4212)
pValue
Symptomatic hypotension
14.0%
9.2%
<0.001
Serum potassium > 6.0 mmol/L
4.3%
5.6%
0.007
Serum creatinine ≥ 2.5 mg/dL
3.3%
4.5%
0.007
Cough
11.3%
14.3%
<0.001
10.7%
12.3%
0.03
Discontinuation for hypotension
0.9%
0.7%
0.38
Discontinuation for hyperkalemia
0.3%
0.4%
0.56
Discontinuation for renal impairment
0.7%
1.4%
0.002
Medications, no hospitalization
6 (0.1%)
4 (0.1%)
0.52
Hospitalized; no airway compromise
3 (0.1%)
1 (<0.1%)
0.31
0
0
—
Prospectively identified adverse events
Discontinuation for adverse event
Angioedema (adjudicated)
Airway compromise
McMurray JJV, et al. N Engl J Med. 2014;371:993-1004.
New FDA-Approved Sacubitril/Valsartan
Sacubitril/Valsartan
Brand name
Entresto
Indication
The fixed-dose combination of the neprilysin inhibitor sacubitril and
the ARB valsartan is indicated to reduce the risk of CV death and HF
hospitalization in patients with HF with reduced ejection fraction.
Dosage
Start with 49/51 mg twice daily. Double the dose after 2–4 weeks as
tolerated to maintenance dose of 97/103 mg twice daily.
Renal/hepatic
impairment
For patients not currently taking an ACEI or ARB, or for those with
severe renal impairment (eGFR <30 mL/min/1.73 m2) or moderate
hepatic impairment, start with 24/26 mg twice daily.
Switching from an
ACE inhibitor
Stop ACE inhibitor for 36 hours before starting treatment.
Contraindications
History of angioedema related to previous ACE inhibitor or ARB,
concomitant use of ACE inhibitors, concomitant use of aliskiren in
patients with diabetes. WARNING – pregnancy, hyperkalemia.
Side effects
Hypotension, hyperkalemia, cough, dizziness, renal failure, and
angioedema (0.5% Sac/Val vs. 0.2% Enalapril).
http://www.pdr.net/full-prescribing-information/entresto?druglabelid=3756. Accessed October 20, 2015.
Practical Points on Use of Sacubitril/Valsartan
•
Starting dose is 24/26 mg twice daily, unless patient is currently tolerating full
dose ACEI or ARB in which case start 49/51 mg twice daily
•
Target dose is 97/103 mg twice daily
•
After 2-4 weeks uptitrate to next dose with ultimate goal to achieve target dose
•
Monitor SBP, renal function and K as you would with ACEI or ARB use
•
Space out dosing from other vasoactive medications if needed
•
Adjust diuretics doses based on volume status
Ivabradine
• Acts by inhibiting the If channel,
present in the cardiac SA node
• Reduces persistently elevated heart
SA node
rate
• Evaluated as treatment of HFrEF who
have a resting HR of at least 70 beats
per minute, in sinus rhythm, and who
are also taking the highest tolerable
dose of a beta blocker
DiFrancesco D. Curr Med Res Opin. 2005;21:1115-1122.
SHIFT Study: Primary Endpoint of CV Death or Hospitalization for
Worsening HF
Patients with
Primary Endpoint (%)
40
Ivabradine (n=3241)
Placebo (n=3264)
30
Placebo
937 events (29%)
−18%
Ivabradine
793 events (24%)
20
HR 0.82 (95% CI, 0.75–0.90)
p<0.0001
ARR = 5%, NNT = 20
10
0
0
6
12
18
Months
24
30
Swedberg K, et al. Lancet. 2010;376:875-885.
SHIFT Study: Effect of Ivabradine on Outcomes
Ivabradine
(n=3241)
Placebo
(n=3264)
HR
p-Value
Primary endpoint
24%
29%
0.82
<0.0001
All-cause mortality
16%
17%
0.90
0.092
Death from HF
3%
5%
0.74
0.014
All-cause hospitalization
38%
42%
0.89
0.003
Any CV hospitalization
30%
34%
0.85
0.0002
CV death, hospitalization
for worsening HF, or
hospitalization for
non-fatal MI
25%
30%
0.82
<0.0001
Endpoint
Swedberg K, et al. Lancet. 2010;376:875-885.
New FDA-Approved Ivabradine
Ivabradine
Brand name
Corlanor
Indication
To reduce the risk of hospitalization for worsening HF in patients with
stable, symptomatic chronic HF with LVEF ≤ 35% who are in sinus
rhythm with resting HR ≥70 bpm and either are on maximally tolerated
doses of beta-blockers or have a contraindication to beta-blocker use.
Dosage
Start with 5 mg twice daily. After 2 weeks of treatment, adjust dose
based on HR. Max is 7.5 mg twice daily. In patients with conduction
defects or in whom bradycardia could lead to hemodynamic
compromise, start with 2.5 mg twice daily.
Contraindications
Acute decompensated HF; BP <90/50 mmHg; sick sinus syndrome or
third-degree AV block, unless a functioning demand pacemaker is
present; resting HR < 60 bpm prior to treatment; severe hepatic
impairment; pacemaker dependence. WARNING – fetal toxicity.
Side effects
Occurring in ≥1% of patients are bradycardia, hypertension, atrial
fibrillation, and luminous phenomena (phosphenes).
http://www.pdr.net/full-prescribing-information/corlanor?druglabelid=3713. Accessed October 20, 2015.
Practical Points on Use of Ivabradine
•
Starting dose is 5 mg twice daily
•
Target HR is 50-60 bpm
•
After 2 weeks:
– If HR >60 bpm:
Increase dose to 7.5 mg twice daily (Max dose)
– If HR 50-60 bpm:
Maintain initial dose
– If HR <50 bpm or symptomatic bradycardia:
Lower dose to 2.5 mg twice daily
– If HR <50 bpm or symptomatic bradycardia and dose is 2.5 mg twice daily: Discontinue
Pharmacologic Treatment for
Stage C HFrEF
Strategies:
HFrEF Stage C
NYHA Class I – IV
Treatment:
Disease Management
Remote PA monitoring
Process Improvement
Patient Education
Frailty Assessment
Palliative Care
Genetic Counseling
Class I, LOE A
ACEI or ARB AND
Beta Blocker
? Valsartan/Sacubutril
? Ivabradine
For all volume overload,
NYHA class II-IV patients
For persistently symptomatic
African Americans,
NYHA class III-IV
For NYHA class II-IV patients.
Provided estimated creatinine
>30 mL/min and K+ <5.0 mEq/dL
Add
Add
Add
Class I, LOE C
Loop Diuretics
Class I, LOE A
Hydral-Nitrates
Class I, LOE A
Aldosterone
Antagonist
New Guidelines Have Emerged- 2016
COR/LOE 2016
RAASi in Heart Failure and Post-MI LV Dysfunction
ACEi1
MRA
ARB1
ARNI3
Post-MI
Low EF
Mild-Mod CHF
Low EF
CHF
Severe HF
CHF
Preserved EF
AIRE
SAVE
SOLVD
CONSENSUS
PEP-CHF
(perindopril)
EPHESUS1
(eplerenone)
EMPHASIS1
(eplerenone)
RALES1
(spironolactone)
TOPCAT2
(spironolactone)
OPTIMAAL
VALIANT
ELITE-II
HEALL
VAL-HeFT
CHARM
CHARM-Preserved
I-PRESERVE
PARADIGM-HF
(LCZ-696)
RAASi=renin-angiotensin-aldosterone inhibitor; MI=myocardial infarction; EF: ejection fraction; CHF=chronic heart failure;
ACEi=angiotensin-converting enzyme inhibitor; MRA=mineralocorticoid receptor antagonist; ARB=angiotensin II receptor
blocker; ARNI=angiotensin receptor-neprilysin inhibitor.
1. Mentz RJ, et al. Int J Cardiol. 2013:167:1677-1687.
2. Pitt B, et al. N Engl J Med. 2014;370(15):1383-1392.
3. McMurray JJV, et al. N Engl J Med 2014;371:993-1004.
RAAS inhibition- 2016
ACE-I & ARB- 2016
ARNI 2016
ARNI – (Harm) 2016
Ivabradine 2016
ESC HF Guidelines 2016
ESC HFrEF Treatment Algorithm
A new classification?
ESC HF GUIDELINES 2016
Definition of Heart Failure- ACC/AHA 2013
Classification
I. Heart Failure with
Reduced Ejection
Fraction (HFrEF)
II. Heart Failure with
Preserved Ejection
Fraction (HFpEF)
Ejection
Fraction
≤40%
≥50%
a. HFpEF, Borderline 41% to 49%
b. HFpEF, Improved
>40%
Description
Also referred to as systolic HF. Randomized clinical trials have
mainly enrolled patients with HFrEF and it is only in these
patients that efficacious therapies have been demonstrated to date.
Also referred to as diastolic HF. Several different criteria have
been used to further define HFpEF. The diagnosis of HFpEF is
challenging because it is largely one of excluding other potential
noncardiac causes of symptoms suggestive of HF. To date,
efficacious therapies have not been identified.
These patients fall into a borderline or intermediate group. Their
characteristics, treatment patterns, and outcomes appear similar to
those of patient with HFpEF.
It has been recognized that a subset of patients with HFpEF
previously had HFrEF. These patients with improvement or
recovery in EF may be clinically distinct from those with
persistently preserved or reduced EF. Further research is needed
to better characterize these patients.
Yancy C et al, JACC 2013
From: Characteristics and Outcomes of Adult Outpatients With Heart Failure and Improved or Recovered
Ejection Fraction
JAMA Cardiol. Published online July 06, 2016. doi:10.1001/jamacardio.2016.1325
Figure Legend:
Kaplan-Meier Curves, Adjusted for Age and Sex, Across the 3 Heart Failure GroupsThe stratified log-rank χ22 was 15.0 (P < .001)
for difference in mortality between groups. HFpEF indicates heart failure with preserved ejection fraction; HFrecEF, heart failure with
recovered ejection fraction; and HFrEF, heart failure with reduced ejection fraction.
Date of download: 7/11/2016
Copyright © 2016 American Medical
Association. All rights reserved.
A new HF phenotype 2016
From: Potential Mortality Reduction With Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor
Therapy in Heart Failure
JAMA Cardiol. Published online June 22, 2016. doi:10.1001/jamacardio.2016.1724
Table Title:
Demonstrated Benefits of Evidence-Based Therapies for Patients With Heart Failure and Reduced Ejection Fraction
Date of download: 7/11/2016
Copyright © 2016 American Medical
Association. All rights reserved.
Taking the failure out of HF - 2016
•
We can prevent the progression of HF
–
Greater use of biomarkers & imaging – PREVENTION, diagnosis, prognosis & treatment ;early introduction of
RAAS inhibitors
•
•
GDMT for HFrEF & Quality Improvement
–
Still with untapped effectiveness
–
Device therapy (ICD/CRT) as indicated; now incl PA monitor?
New drug therapies–
LCZ696; Ivabradine
• Personalized Therapy driven by Pharmacogenomics
• - NO donors
•
Reversal of Disease
–
Stem cells (iPS, mesenchymal); Gene Transfer; Growth Factors
–
Gene Editing
Questions?
Thank you!
8/2/2016
©2013, American Heart Association
38
More Questions about Get With The Guidelines?
Visit heart.org/QualityHF to find your local Get With The Guidelines representative.
Liz Olson, CVA
Program Manager
Get With The Guidelines® - Resuscitation & Heart Failure
[email protected] I www.heart.org
Phone 214-706-1528
©2013, American Heart Association
39